This proposal requests support for the purchase of an LC/MS system to augment the capabilities of the Mass Spectrometry Facility at Roswell Park Cancer Institute. The instrument requested is a Finnigan LCQ/TM ion trap benchtop mass spectrometer with electrospray (ESI) and atmospheric pressure chemical ionization (APCI) sources. Funds are also sought for a matching HPLC system, P4000-040 quaternary gradient system with UV/VIS detector and membrane degasser (from Thermo Separation Products, NJ) and a nanoelectrospray ion source (Protein Analysis Company, Odense, Denmark). The Finnigan LCQ/TM system has a 0-2000 dalton mass range analyzer and LC/MS/MS/n capabilities. The system is controlled by a PC with Microsoft Windows NT operating system. The biochemistry software is used for molecular weight determination from multi-charged ion envelope operated by ESI, peptide mapping of proteolytic digests and peptide sequence prediction and conformation. The Finnigan LCQ/TM LC/MS system will provide much needed analytical services to eleven NIH-funded investigators and two NIH funded research groups. It will be used to characterize proteins and peptide by their molecular weight, amino acid sequence, disulfide linkages and covalent and other modifications. This system will also be used to study oligonucleotides, oligosaccharides, drug metabolites, nucleic acid metabolites, etc. The LCQ/TM system will permit qualitative and quantitative studies using LC/MS, a technique not currently available at RPCI. LC/MS using selected ion monitoring via MS/MS techniques will be important for on-line quantitation of drug metabolites, oxidatively damaged oligonucleotides, nucleic acid metabolites, etc., at very low levels in complex biological matrices.